CAL2 enables reliable distinction of CALR mutated ET and PMF from PV and reactive bone marrow alterations.
MPNs – Myeloproliferative Neoplasms / ET – Essential Thrombocythaemia / PMF – Primary Myelofibrosis / PV – Polycythaemia Vera
Diagnostic significance of CALR mutations in relation to JAK2 and MPL mutations in MPNs
CALR mutations are detectable in 67% of ET and 88% of PMF cases with non-mutated JAK2 or MPL. It is mutually exclusive with mutations of JAK2 or MPL in MPNs: The detection of CALR mutations fills a diagnostic gap in ET and PMF patients harbouring non-mutated JAK2/MPL.
References:
Klampfl T et al. Somatic Mutations of Calreticulin in myeloproliferative Neoplasms. N Engl J Med 369(25): 2379-2390, 2013
Nangalia J et al. Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2. N Engl J Med 369(25): 2391-2405, 2013
CAL2 staining of megakaryocytes with & without CALR mutations
CAL2 IHC of four MPN cases:
A and C: Selective staining of mutated CALR protein in megakaryocytes of essential thrombocythaemia (A) and early primary myelofibrosis (C).
B and D: Absent CAL2 staining in two essential thrombocythaemia cases with molecularly detected mutation in JAK2 (B) and MPL (D).
CAL2 IHC of four PMF cases:
A and C: Selective staining of mutated CALR protein in megakaryocytes of two PMF cases, respectively in prefibrotic phase and in fibrotic phase, in which Sanger sequencing detectd a CALR mutation.
B and D: Absent CAL2 staining in two PMF cases, respectively in prefibrotic and fibrotic phase, both without molecularly detected mutated CALR. The fibrotic stroma remains unstained (C and D).
Application of CAL2 monoclonal antibody
CAL2 antibody immunohistochemistry (IHC) is suitable for
- a specific, sensitive, rapid and cost-effective identification of different types of CALR mutations in FFPE bone marrow sections
- excluding JAK2 mutation and therefore diagnosis of PV
- indication for molecular analysis of CALR mutation for distinguishing type 1 and 2 mutations
Why is CAL2 able to detect all known types of CALR mutations ?
All different types of CALR mutations result in a novel C-terminus. This harbours a common epitope expressed in all different types of CALR mutations. The CAL2 antibody is directed against this common epitope. Therefore, it can be concluded that CAL2 antibody is able to detect all CALR mutations.